Preliminary study of the role of nanobacteria in the formation of renal stones in experimental rats and its mechanism.

Introduction: The aim of the study was to study the role of nanobacteria in the formation of renal calculi and the underlying mechanism. Material and methods: A total of 90 clean Wistar male rats were randomly divided into a negative control group, an experimental group, and an interference group. From the end of the first week of modelling, 10 consecutive times once a week, 3 rats in each group were randomly selected to measure the biochemical blood markers and urine metabolism. After sacrifice, the formation of kidney stones was assessed by observing the ultrastructure of the kidney by electron microscopy and pathohistology. Finally, the expression of calcium-sensitive receptor (CaSR) and claudin-14 protein in the kidney tissue was examined by western blotting. Results: Compared with the control group, the gross structure of the kidney was changed in the model group. At the fourth week of modelling, the rats in the nanobacteria group had significantly enlarged kidneys and increased kidney-to-body ratio, and the difference had statistical significance (p < 0.05). The colour of the kidney profile was dark, the structure of the skin pulp was less clear, and the accumulation of yellowish particles was observed at the junction of the cortical pulp. The creatinine, uric acid, urea nitrogen, and urinary calcium of the rats in the nanobacteria group began to increase at the third week, and the difference between the third and eighth week had statistical significance (p < 0.05). However, the difference between the 3 groups had no statistical significance after the eighth week. At the fourth week, we observed the formation of calculi, which were mainly distributed in the renal tubules and surrounding tissues. The kidney stone formation rate was 52.4% in the nanobacteria group and 27.8% in the interference group, and the difference had statistical significance (p < 0.05). Ultrastructure observations revealed that from the fourth week, the renal tissues in the nanobacteria group showed expanded renal tubules, swollen renal tubular epithelium, granular degeneration, shedding and lymphocyte infiltration of renal tubular epithelial cells, and a small amount of calcium salt crystals in renal tubules. At the third week, the expression of CaSR and Claudin-14 protein in the nanobacteria group increased, and the difference had statistical significance (p < 0.05). The expression of CaSR and Claudin-14 was positively correlated with urinary calcium (p < 0.05). Conclusions: The formation of renal calculi began in the fourth week after the model was established, and the crystals were mostly located in the renal tubules. During the formation of renal calculi, the renal tubular epithelial cells were damaged, showing granular degeneration and small amounts of calcium salt crystals, accompanied by a few renal tubules beginning to expand and epithelial swelling, granular degeneration, necrosis and shedding of renal tubular epithelial cells, lymphocyte infiltration in the renal interstitium, and small amounts of calcium salt crystals in the renal tubules, which aggravated with time. The serum creatinine, serum uric acid, urea nitrogen, and urinary calcium levels increased with time from the third week and returned to normal after the eighth week. The expression of CaSR and Claudin-14 protein was upregulated and positively correlated with the 24-h urinary calcium excretion value.

Disruption of Autophagic Flux and Treatment with the PDPK1 Inhibitor GSK2334470 Synergistically Inhibit Renal Cell Carcinoma Pathogenesis.

Background: Renal cell carcinoma (RCC) frequently exhibits activating PI3K-Akt-mTOR pathway mutations. 3-Phosphoinositide-dependent kinase 1 (PDPK1 or PDK1) has been established to play a pivotal role in modulating PI3K pathway signaling. mTOR is the main autophagy-initiating factor. However, limited advances have been made in understanding the relationship between PDPK1 and autophagy in RCC. Methods: GSK2334470 (GSK470), a novel and highly specific inhibitor of PDPK1, was selected to investigate the anticancer effects in two RCC cell lines. Cell growth was assessed by CCK-8 test and colony formation. Changes in the protein levels of key Akt/mTOR pathway components and apoptosis markers were assessed by Western blotting. Autophagy was assessed by using LC3B expression, transmission electron microscopy, and a tandem mRFP-EGFP-LC3 construct. The effect of PDPK1 and autophagy inhibitor chloroquine in RCC in vivo was examined in a mouse tumor-bearing model. Results: GSK470 significantly inhibited cell proliferation and induces apoptosis in A498 and 786-O RCC cells. GSK470 downregulates the phosphorylation of PDPK1, thereby inhibiting downstream phosphorylation of Akt1 at Thr308 and Ser473 and mTOR complex 1 (mTORC1) activity. Treatment with insulin-like growth factor-1 (IGF-1) partially restored GSK470-induced behaviors/activities. Interestingly, treatment of A498 and 786-O cells with GSK470 or siPDPK1 induced significant increases in the hallmarks of autophagy, including autophagosome accumulation, autophagic flux, and LC3B expression. Importantly, GSK470 and chloroquine synergistically inhibited the growth of RCC cells in vitro and in xenograft models, supporting the protective role of autophagy activation upon blockade of the PDPK1-Akt-mTOR signaling pathway. Conclusion: Our study provides new insight into PDPK1 inhibition combined with autophagy inhibition as a useful treatment strategy for RCC.

A lightweight bladder tumor segmentation method based on attention mechanism.

In the endoscopic images of bladder, accurate segmentation of different grade bladder tumor from blurred boundary regions and highly variable shapes is of great significance for doctors' diagnosis and patients' later treatment. We propose a nested attentional feature fusion segmentation network (NAFF-Net) based on the encoder-decoder structure formed by the combination of weighted pyramid pooling module (WPPM) and nested attentional feature fusion (NAFF). Among them, WPPM applies the cascade of atrous convolution to enhance the overall perceptual field while introducing adaptive weights to optimize multi-scale feature extraction, NAFF integrates deep semantic information into shallow feature maps, effectively focusing on edge and detail information in bladder tumor images. Additionally, a weighted mixed loss function is constructed to alleviate the impact of imbalance between positive and negative sample distribution on segmentation accuracy. Experiments illustrate the proposed NAFF-Net achieves better segmentation results compared to other mainstream models, with a MIoU of 84.05%, MPrecision of 91.52%, MRecall of 90.81%, and F1-score of 91.16%, and also achieves good results on the public datasets Kvasir-SEG and CVC-ClinicDB. Compared to other models, NAFF-Net has a smaller number of parameters, which is a significant advantage in model deployment.

Geriatric nutritional risk index as a prognostic factor in elderly patients with non-muscle-invasive bladder cancer: a propensity score-matched study.

PURPOSE: The Geriatric Nutrition Risk Index (GNRI) is a simple and validated tool used to assess the nutritional status of elderly patients and predict the risk of short-term postoperative complications, as well as the long-term prognosis, after cancer surgery. In this study, we aimed to evaluate the predictive value of GNRI for the long-term postoperative prognosis in elderly patients with primary non-muscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). METHODS: We retrospectively analyzed data from 292 elderly patients with primary NMIBC. Using X-tile software, we divided the cohort into two groups based on GNRI and determined the cut-off value for postoperative recurrence-free survival (RFS). Propensity score matching (PSM) with a ratio of 1:3, Kaplan-Meier analysis, log-rank test, and COX proportional hazards regression were used to assess the correlation between GNRI and prognosis and identify factors predicting recurrence and progression. RESULTS: In the entire cohort, the 3 year recurrence group had significantly lower GNRI compared to the 3 year non-recurrence group (P = 0.0109). The determined GNRI cut-off value was 93.82. After PSM, the low GNRI group had significantly lower RFS (P < 0.0001) and progression-free survival (PFS) (P = 0.0040) than the high GNRI group. Multivariate COX regression showed that GNRI independently predicted RFS (HR 2.108; 95% CI 1.266-3.512; P = 0.004) and PFS (HR 2.155; 95% CI 1.135-4.091; P = 0.019) in elderly patients with primary NMIBC. CONCLUSION: Preoperative GNRI is a prognostic marker for disease recurrence and progression in elderly patients with primary NMIBC undergoing TURBT.

Comparison of novel flexible and traditional ureteral access sheath in retrograde intrarenal surgery.

OBJECTIVES: To compare the efficiency and safety of a novel flexible ureteral access sheath (f-UAS) and traditional ureteral access sheath (UAS) during retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Between January 2022 and September 2022, a total of 152 consecutive cases with renal stones underwent RIRS with the f-UAS. Their outcomes were compared with those of another 152 consecutive cases undergoing RIRS with traditional UAS using a 1:1 scenario matched-pair analysis, with matching parameters including age and stone size. The f-UAS is a novel UAS with a 10-cm-long tube at the tip that can follow the bends of flexible ureteroscope (f-URS). RESULTS: Baseline characteristics were found to be similar between the two groups. The f-UAS group demonstrated significantly higher SFR (76.3% vs. 7.2%; P < 0.001) at 1 day postoperatively and a higher clearance rate of stone volume (98.11% vs. 91.78%; P < 0.001). The f-UAS group also had lower total complications rate (9.9% vs. 22.4%; P = 0.003), lower incidence of fever (5.9% vs 11.9%; P = 0.001), shorter operative times (56.5 min vs. 59.9 min; P = 0.047), and lower usage rate of baskets (17.1% vs. 100%; P < 0.001). There was no significant difference in SFR at 1 month postoperatively (P = 0.627) and in the length of postoperative hospital stay between the two groups (P = 0.225). CONCLUSION: Compared to the traditional UAS during RIRS, the f-UAS showed several advantages, including higher SFR at 1 day postoperatively, shorter operative times, lower incidence of complications, and less use of basket.

Flexible ureteroscopy with novel flexible ureteral access sheath versus mini-percutaneous nephrolithotomy for treatment of 2-3 cm renal stones.

OBJECTIVES: To assess and compare the effectiveness and safety of flexible ureteroscopy (f-URS) with a novel flexible ureteral access sheath (f-UAS) versus mini-percutaneous nephrolithotripsy (mini-PCNL) in treating 2-3 cm renal stones. METHODS: Retrospectively analyzed consecutive cases that underwent f-URS with f-UAS (12/14 Fr) from January 29, 2022, to November 30, 2022. Consecutive cases that underwent mini-PCNL (18 Fr) from June 5, 2021, to January 26, 2022, were selected as controls. The f-UAS is a novel device with a 10 cm anterior tip that passively bends along with the f-URS to enter the renal calyx. We analyzed demographic characteristics, stone parameters, operative time, stone-free rates (SFR), hospitalization time, and complication. RESULTS: A total of 96 consecutive cases that underwent f-URS with f-UAS and 96 consecutive cases that underwent mini-PCNL were included in the study. There were no significant differences between the two groups in terms of operative time (p = 0.06), stone volume clearance (p = 0.533) and complete SFR (p = 0.266) on the first postoperative day or residual Stone after 1 month (p = 0.407). We observed a significantly shorter postoperative hospital stay (1.4 days vs. 2.1 days; p < 0.001) and a lower decrease in hemoglobin levels (0.39 g/dL vs. 0.68 g/dL; p < 0.001) in the f-UAS group. The mini-PCNL group had a significantly higher overall complication rate (13.5%) compared with the f-UAS group (5.2%; p = 0.048). CONCLUSIONS: In the treatment of 2-3 cm renal stones, f-URS with a novel f-UAS may provide a superior alternative to mini-PCNL, potentially challenging its established status.

Optimal placement of flexible ureteral access sheath in retrograde intrarenal surgery.

This study aims to explore the optimal location of flexible ureteral access sheath (f-UAS) in retrograde intrarenal lithotripsy (RIRS). RIRS model was built by AutoCAD 2011 software, and imported COMSOL 5.6 software to computer simulation. An RIRS model was constructed in vitro to analyze the distribution pattern of stone fragments and compare the weight of stone fragments carried out by the irrigation fluid when the f-UAS is in different positions. Computer simulation showed that the highest flow of irrigation fluid was in the channel of flexible ureteroscopy (f-URS) and in the lumen of f-UAS. From the f-URS to the renal collection system and then to the f-UAS, the velocity of irrigation fluid changes gradually from high-flow to low-flow and then to high-flow. When the f-URS and the f-UAS are at the same level, the irrigation fluid is always at a state of high flow during the process from f-URS to f-UAS. When the f-URS and the f-UAS are at the same level, it can increase the local intrarenal pressure (IRP) at the front of f-URS. The stone fragments are mainly sediment in the low-flow region of irrigation fluid. More stone fragments could follow the irrigation fluid out of the body when the tip of f-URS and the tip of f-UAS are at the same level (P < 0.001). The f-UAS should be brought closer to the stone in RIRS. And more stone fragments can be taken out of the body by the effect of irrigation fluid.

Initial experience and short-term outcomes of single-port extraperitoneal transvesical robot-assisted radical prostatectomy: a two-center study.

Background: This study presents the procedure of single-port extraperitoneal transvesical approach to robot-assisted radical prostatectomy (SETvRARP) on the da Vinci Xi platform coupling with a 4-channel single port and evaluated the short-term outcomes in the first 72 prostate cancer (PCa) patients. Methods: Seventy-two patients with localized PCa were enrolled. Each operation was conducted by the same single robotic surgery group in two centers using the da Vinci Xi system. Results: The median operation time was 150 min, and the median estimated blood loss was 50 mL. All operations were successfully carried out without open conversion or transfusion. No ≥ Grade II complications were noted. Urethral catheters were routinely removed on postoperative day 7. Sixty-eight (94.4%) patients recovered to immediate urinary continence after surgery, with 72 (100%) patients achieving full continence on postoperative day 14. A positive surgical margin was observed in 15 (20.8%) patients. Postoperative urodynamic studies regarding peak urinary flow, bladder capacity, and residual urine were not statically different from the preoperative results. No biochemical recurrence was noted in all patients within the follow-up period. Postoperative erectile function was not statistically different from the preoperative results (P=0.1697). Conclusions: SETvRARP using the da Vinci Xi system coupling with a 4-channel single port is a valid radical prostatectomy technique in well-selected PCa patients, resulting in superior postoperative recovery of urinary continence. Meanwhile, the outcomes in functional protection and cancer control need to be further investigated with a long-term follow-up duration.

Development and validation of a prognostic model incorporating tumor thrombus grading for nonmetastatic clear cell renal cell carcinoma with tumor thrombus: A multicohort study.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole-exome sequencing on normal-tumor-thrombus-metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C-index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501-0.610, 0.667 versus 0.544-0.651, and 0.719 versus 0.511-0.700 for Training, China-Validation, and Poland-Validation cohorts, respectively). We constructed a risk predicting model, TT-GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT-GPS score displayed better discriminatory ability (OS, c-index: 0.706-0.840, AUC: 0.788-0.874; DFS, c-index: 0.691-0.717, AUC: 0.771-0.789) than previously reported models in risk assessment. In conclusion, we identified for the first-time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT-GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Downregulation of RAB17 have a poor prognosis in kidney renal clear cell carcinoma and its expression correlates with DNA methylation and immune infiltration.

BACKGROUND: RAB17 is one of the RAB family members. It has been reported to be closely associated with a variety of tumors and has different roles in various tumors. However, the effect of RAB17 in KIRC remains unclear. MATERIALS AND METHODS: We analyzed the differential expression of RAB17 in kidney renal clear cell carcinoma (KIRC) tissues and normal tissues using the public databases. The prognostic role of RAB17 in KIRC was analyzed using the Cox regression methods, and a prognostic model was constructed based on the results of the Cox analysis. In addition, further analysis of RAB17 in KIRC was performed in relation to genetic alterations, DNA methylation m6A methylation and immune infiltration. Finally, RAB17 mRNA and protein expression levels were analyzed in tissue samples (KIRC tissues and normal tissues) and cell lines (normal renal tubular cell and KIRC cells), and in vitro functional assays were performed. RESULTS: RAB17 was low-expressed in KIRC. Downregulation of RAB17 expression is correlated with unfavorable clinicopathological characteristics and a worse prognosis in KIRC. The RAB17 gene alteration in KIRC was primarily characterized by copy number alteration. Six CpG sites of RAB17 DNA methylation levels are higher in KIRC tissues than in normal tissues, and are correlated with RAB17 mRNA expression levels, showing a significant negative correlation. cg01157280 site DNA methylation levels are associated with pathological stage and overall survival, and it may be the only CpG site with independent prognostic significance. Functional mechanism analysis revealed that RAB17 is closely associated with immune infiltration. RAB17 expression was found to be negatively correlated with most immune cell infiltration according to two different methods. Furthermore, most immunomodulators were significantly negatively correlated with RAB17 expression, and significantly positively correlated with RAB17 DNA methylation levels. RAB17 was significantly low expression in KIRC cells and KIRC tissues. In vitro, silencing of RAB17 promoted KIRC cell migration. CONCLUSION: RAB17 can be used as a potential prognostic biomarker for patients with KIRC and for assessing immunotherapy response.

[Corrigendum] Celecoxib inhibits the epithelial­to­mesenchymal transition in bladder cancer via the miRNA­145/TGFBR2/Smad3 axis.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the Transwell migration assays shown in Figs. 1B and 3B on p. 685 and p. 688 respectively, the images selected for the '5637 / DMSO' experiment in Fig. 1B and the DMSO experiment in Fig. 3B were apparently the same, such that these data appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that the 5637 DMSO data panel in Fig. 3B had been selected incorrectly. The revised version of Fig. 3, showing the correct data for the DMSO experiment in Fig. 3B, is shown on the next page. The authors regret that these errors went unnoticed prior to the publication of this article, and thank the Editor of International Journal of Molecular Medicine for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused. [International Journal of Molecular Medicine 44: 683­683, 2019; DOI: 10.3892/ijmm.2019.4241].

Robotic-assisted laparoscopic adrenalectomy (RARLA): What advantages and disadvantages compared to retroperitoneal laparoscopic adrenalectomy (RLA)?

Objective: To explore the advantages and disadvantages of robot-assisted laparoscopic adrenalectomy compared with retroperitoneal laparoscopic adrenalectomy. Methods: A total of 101 patients with adrenal tumors who received retroperitoneal laparoscopic adrenalectomy (RLA) (n=75) or robot-assisted laparoscopic adrenalectomy (RARLA) (n=26) in our hospital from January 2021 to December 2021 were retrospectively collected. Patients' demographics, tumor characteristics, and perioperative indicators were compared. Statistical analysis was performed using t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. Results: We found that blood loss in the RARLA group was significantly less than that in the RLA group (66.9 ± 35.5 ml vs 91.5 ± 66.1 ml, p = 0.020). Gastrointestinal function recovery time in RARLA group was significantly less than that in RLA group (19.9 ± 6.9 hours vs 32.0 ± 9.0 hours, p < 0.001). However, the operation time, drainage tube placement time, post-operative hospital stay in the RARLA group were significantly longer compared with the RLA group (149.6 ± 53.4 mins vs 118.7 ± 41.2 mins, p = 0.003; 4.9 ± 2.0 days vs 3.6 ± 1.1 days, p = 0.004; 6.4 ± 1.8 days vs 4.6 ± 1.6 days, p < 0.001). The hospitalization expense in the RARLA group is significantly higher than that in the RLA group (59284 ± 8724 RMB¥ vs 39785 ± 10126 RMB¥, p < 0.001). We found that there was no significant difference in the incidence of postoperative complications between the two groups. However, the pathological types of the two groups were significantly different. Patients in the RLA group had a higher proportion of adrenocortical adenoma, while patients in the RARLA group had a higher proportion of pheochromocytoma. Conclusion: Compared with traditional laparoscopic adrenalectomy, robot-assisted laparoscopic adrenalectomy can significantly reduce intraoperative blood loss and accelerate postoperative gastrointestinal recovery. It is committed to studying how to reduce the hospitalization time and hospitalization cost of RARLA, which can make RARLA more widely used.

IGF2BP3 overexpression predicts poor prognosis and correlates with immune infiltration in bladder cancer.

BACKGROUND: IGF2BP3 expression is associated with poor prognosis in cancers of multiple tissue origins. However, the precise mechanism of its co-carcinogenic action in bladder cancer is unknown. METHODS: We aimed to demonstrate the relationship between IGF2BP3 expression and pan-cancer using The Cancer Genome Atlas (TCGA) database. We next validated IGF2BP3 expression in the Gene Expression Omnibus (GEO) database (GSE3167). Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic values of IGF2BP3. Cox and logistic regression were used to explore the factors affecting the prognosis. Protein-protein interactions (PPIs) network was constructed by STRING. Enrichment analyses were performed to infer involved pathways and functional categories of IGF2BP3 using the cluster Profiler package. We applied single-sample gene set enrichment analysis (ssGSEA) algorithm and TIMER database to evaluate the expression level of immune genes. RESULTS: Pan-cancer analyses reveal that IGF2BP3 was higher in most cancer types, including bladder cancer, and the same results were found in GSE3167. The area under the ROC curve of IGF2BP3 was 0.736, which indicated that IGF2BP3 may be a potential diagnostic biomarker. High IGF2BP3 expression was associated with poorer overall survival (OS) (P = 0.015). For validation, we collected 95 bladder cancer samples and found that IGF2BP3 expression was higher in bladder cancer tissues than that in non-tumor bladder tissues by immunohistochemistry staining. We found a positive correlation between the expression level of IGF2BP3 and the clinical stage of bladder cancer. Immunocyte infiltration analysis showed that high IGF2BP3 expression was correlated with regulating the infiltration level of immune cell, including neutrophil cells and macrophages. IGF2BP3 promotes migration and invasion of bladder cancer cells, while IGF2BP3 inhibition had the opposite effects. Higher IGF2BP3 expression was closely associated with advanced TNM stage. CONCLUSION: IGF2BP3 overexpression was related to disease progression and poor prognosis, as well as infiltration of immune cells in bladder cancer. IGF2BP3 can be a promising independent prognostic biomarker and potential treatment target for bladder cancer.

For small (1-3cm) nonfunctional adrenal incidentaloma (NFAI), which option is more appropriate for conservative treatment or surgery?

Objective: To compare the efficacy and safety between conservative treatment and surgery for the patients with small (1-3cm) nonfunctional adrenal incidentaloma (NFAI). Methods: The patients with small (1-3cm) NFAI who received conservative treatment or surgery in our hospital from November 2018 to December 2019 were retrospectively collected. A total of 83 patients were included in this study. They were divided into two groups according to the treatment methods: the surgery group (n=51) and the conservative treatment group (n=32).Then patients' demographics, tumor characteristics, functional indicators and complications were compared. Statistical analysis was performed using t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. Results: At the time of diagnosis, after 3 months, after 6 months, after 12 months, and after 24 months, we found that there was no significant difference between the two groups in systolic blood pressure, diastolic blood pressure, serum potassium levels, and hormone levels. 51 patients chose to have surgery, of which 41 patients chose RLA and 10 patients chose RARLA. RARLA group patients had the highest total cost and conservative treatment group patients had the lowest cost, and the difference was significant (P < 0.001). There was no significant difference in tumor size in the conservative treatment group between at the time of diagnosis and after 24 months (P = 0.305). Conclusion: Surgical treatment is more effective for 1-3cm NFAI, but conservative treatment is safer and more economical. Follow-up after conservative or surgical treatment is necessary.

Assessment of oligometastasis status of prostate cancer following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone using PSA percentage decline rate.

Objective: To compare the tumor control in prostate cancer patients with oligo-metastasis following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone based on total prostate-specific antigen (tPSA) assessment. Methods: Medical data of a total of 18 prostate cancer patients with oligometastasis administered in The First Affiliated Hospital of Nanchang University from March 2017 to March 2018 were prospectively collected. 10 patients received a combined therapy of robot-assisted radical prostatectomy and pharmaceutical androgen deprivation (RARP+ADT group), while 8 patients received pharmaceutical androgen deprivation therapy alone (ADT group). Then demographic characteristics, prostate volume, tumor characteristics and tPSA data were analysised and compared. Statistical analysis was performed using t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. Results: No significant difference was found in patients' age (p = 0.075), prostate volume (p = 0.134) and number of bone metastasis (p = 0.342). Pre-treatment Gleason score was significantly lower in RA group (p = 0.003). Patients in RARP+ADT group had significantly lower pre-treatment tPSA (p = 0.014), while no statistical difference was noted in reexamined tPSA (p = 0.140) on follow-up. No statistical difference was noted in tPSA decline rates (declined tPSA value per day) in RARP+ADT and ADT group (8.1 ± 4.7 verse 7.5 ± 8.0 ng/ml/d, p = 0.853). However, tPSA percentage decline rate (declined tPSA percentage per day) was significantly higher in RARP+ADT group (11.6 ± 1.5%/d verses 2.9 ± 2.2%/d, p< 0.001). Immediate urinary continence was achieved in 9 patients (90%) upon removal of urethral catheter on post-operative day 7 in RARP+ADT group. Conclusion: ADT alone and in combination with RARP both provide effective tumor control in patients suffering from prostate cancer with oligometastasis. ADT combined with RARP exhibited significant advantage in PSA percentage decline rate without compromising patients' urinary continence. Long-term tumor control requires further follow-up.

Novel cuproptosis-related long non-coding RNA signature to predict prognosis in prostate carcinoma.

BACKGROUND: Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function. METHODS: RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships. RESULTS: The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan-Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed. CONCLUSIONS: A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.

Efficacy and safety of vorolanib plus everolimus in metastatic renal cell carcinoma: A three-arm, randomised, double-blind, multicentre phase III study (CONCEPT).

BACKGROUND: Vorolanib is a highly potent tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor. This three-arm, randomised, registered study aimed to assess the combination of vorolanib and everolimus or vorolanib alone versus a control arm of everolimus as second-line treatment in patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with advanced or metastatic RCC who had received one prior VEGFR-TKI were randomised (1:1:1) to receive the combination of vorolanib and everolimus or either monotherapy. Patients with brain metastases were excluded. The primary end-point was progression-free survival (PFS) assessed by the independent review committee per Response Evaluation Criteria in Solid Tumours v1.1. RESULTS: Between 10th March 2017 and 30th May 2019, 399 patients (133 in each group) were enrolled. By the cutoff date (30th April 2020), a significant improvement in PFS was detected in the combination group compared with the everolimus group (10.0 versus 6.4 months; hazard ratio, 0.70; P = 0.0171). PFS was similar between the vorolanib group and the everolimus group (median: 6.4 versus 6.4 months; hazard ratio, 0.94; P = 0.6856). A significantly higher objective response rate was observed in the combination group than in the everolimus group (24.8% versus 8.3%; P = 0.0003), whereas there was no significant difference between the vorolanib group and the everolimus group (10.5% versus 8.3%; P = 0.5278). The overall survival data were immature. A total of 96 (72.2%), 52 (39.1%) and 71 (53.4%) grade 3 or higher treatment-related adverse events occurred in the combination group, vorolanib group and everolimus group, respectively. CONCLUSIONS: The addition of vorolanib to everolimus as 2nd-line treatment for patients with advanced or metastatic RCC who have experienced cancer progression after VEGFR-TKI therapy provided a better objective response rate and PFS than everolimus alone with a manageable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03095040; Chinadrugtrials, CTR20160987.

The ADRENAL score: A comprehensive scoring system for standardized evaluation of adrenal tumor.

Objectives: To propose an original and standardized scoring system to quantify the functional and anatomical characteristics of adrenal tumor. Materials and methods: Four groups of consecutive adrenalectomies (n = 458) with heterogeneity in tumor characteristics and surgical approaches, including 212 laparoscopic cases (Group 1) and 105 robotic cases (Group 2) from The First Affiliated Hospital of Nanchang University, 28 robotic cases from Temple University Hospital (Group 3) and 113 laparoscopic cases from The First Affiliated Hospital of Guangxi Medical University (Group 4). All patients were followed up for 4.5 to 5.5 years. Six parameters including functional status or suspicion of malignancy, tumor size, relationship to adjacent organs, intratumoral enhancement on CT, nearness of the tumor to major vessels and body mass index were assessed and scored on a 0, 1 and 2 points scale. Correlation between the sum of the 6 scores and tumor laterality (ADRENAL score) verse operative time (OT), estimated blood loss (EBL), perioperative complications, transfusion, conversion and length of hospital stay was analyzed. Results: ADRENAL score was a strong predictor of both OT and EBL in all four groups (p < 0.05 for all tests). In Group 2 and 4, higher ADRENAL score seemed to correlate with longer hospital stay. No statistically significant correlation between ADRENAL score and complication, transfusion or conversion was noted yet. Conclusions: ADRENAL score appears to be a valid predictor of surgical outcomes. It may provide a common reference for adrenal surgery training program, preoperative risk assessment and stratified comparative analysis of adrenal surgeries via different techniques and approaches.

MAPK8IP2 is a potential prognostic biomarker and promote tumor progression in prostate cancer.

BACKGROUND: MAPK8IP2 is one of the JNK-interacting proteins (JIPs) family members, and is involved in the regulation of the JNK and P38 MAPK signaling pathways. MAPK8IP2 has been reported to be closely associated with several cancers. However, the biological function of MAPK8IP2 in prostate cancer (PCa) remains unclear. METHODS: MAPK8IP2 expression in PCa and subgroups of PCa was analyzed by public databases. The prognostic role of MAPK8IP2 in prostate cancer was analyzed using the Cox regression method. The potential mechanism by which MAPK8IP2 affects PCa progression was investigated by utilizing public data, including genetic alteration, DNA methylation, m6A methylation, and immune infiltration data. We further performed in vitro assays to validate the effect of MAPK8IP2 on PCa cell proliferation, migration and invasion. RESULTS: MAPK8IP2 is highly expressed in PCa tissues. Overexpression of MAPK8IP2 is associated with adverse clinicopathological factors and a poor prognosis in PCa. Receiver operating curve analysis showed that MAPK8IP2 can distinguish PCa tissues from non-PCa tissues with a certain accuracy (AUC = 0.814). The MAPK8IP2 genetic alteration rate was 2.6% and MAPK8IP2 alterations correlated with a poor prognosis. We also found that CDK12 and TP53 mutations were associated with MAPK8IP2 expression. The DNA methylation level of MAPK8IP2 was higher in primary tumors than in normal tissues, and the high MAPK8IP2 DNA methylation group of PCa patients had poor survival. Enrichment analysis indicated that MAPK8IP2 was involved in the MAPK signaling pathway. In vitro, knockdown of MAPK8IP2 inhibited PCa cell proliferation, migration and invasion. CONCLUSION: MAPK8IP2 is a potential target for PCa treatment and can serve as a novel biomarker for PCa diagnosis and prognosis evaluation.

Novel amino acid metabolism-related gene signature to predict prognosis in clear cell renal cell carcinoma.

Background: Amino acid metabolism (AAM) deregulation, an emerging metabolic hallmark of malignancy, plays an essential role in tumour proliferation, invasion, and metastasis. However, the expression of AAM-related genes and their correlation with prognosis in clear cell renal cell carcinoma (ccRCC) remain elusive. This study aims to develop a novel consensus signature based on the AAM-related genes. Methods: The RNA-seq expression data and clinical information for ccRCC were downloaded from the TCGA (KIRC as training dataset) and ArrayExpress (E-MTAB-1980 as validation dataset) databases. The AAM-related differentially expressed genes were screened via the "limma" package in TCGA cohorts for further analysis. The machine learning algorithms (Lasso and stepwise Cox (direction = both)) were then utilised to establish a novel consensus signature in TCGA cohorts, which was validated by the E-MTAB-1980 cohorts. The optimal cutoff value determined by the "survminer" package was used to categorise patients into two risk categories. The Kaplan-Meier curve, the receiver operating characteristic (ROC) curve, and multivariate Cox regression were utilised to evaluate the prognostic value. The nomogram based on the gene signature was constructed, and its performance was analysed using ROC and calibration curves. Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were conducted on its potential mechanisms. The relationship between the gene signature and key immune checkpoint, N6-methyladenosine (m6A)-related genes, and sensitivity to chemotherapy was assessed. Results: A novel consensus AMM-related gene signature consisting of IYD, NNMT, ACADSB, GLDC, and PSAT1 is developed to predict prognosis in TCGA cohorts. Kaplan-Meier survival shows that overall survival in the high-risk group was more dismal than in the low-risk group in the TCGA cohort, validated by the E-MTAB-1980 cohort. Multivariate regression analysis also demonstrates that the gene signature is an independent predictor of ccRCC. Immune infiltration analysis highlighted that the high-risk group indicates an immunosuppressive microenvironment. It is also closely related to the level of key immune checkpoints, m6A modification, and sensitivity to chemotherapy drugs. Conclusion: In this study, a novel consensus AAM-related gene signature is developed and validated as an independent predictor to robustly predict the overall survival from ccRCC, which would further improve the clinical outcomes.